CN102276588A - 一种制备拉呋替丁的新工艺 - Google Patents
一种制备拉呋替丁的新工艺 Download PDFInfo
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- CN102276588A CN102276588A CN2011101151363A CN201110115136A CN102276588A CN 102276588 A CN102276588 A CN 102276588A CN 2011101151363 A CN2011101151363 A CN 2011101151363A CN 201110115136 A CN201110115136 A CN 201110115136A CN 102276588 A CN102276588 A CN 102276588A
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- KMZQAVXSMUKBPD-DJWKRKHSSA-N Lafutidine Chemical compound C=1C=COC=1C[S+]([O-])CC(=O)NC\C=C/COC(N=CC=1)=CC=1CN1CCCCC1 KMZQAVXSMUKBPD-DJWKRKHSSA-N 0.000 title claims abstract description 51
- 229960003303 lafutidine Drugs 0.000 title claims abstract description 51
- 238000004519 manufacturing process Methods 0.000 title description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 141
- 238000006243 chemical reaction Methods 0.000 claims abstract description 58
- 238000003756 stirring Methods 0.000 claims abstract description 28
- 238000002360 preparation method Methods 0.000 claims abstract description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 78
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 78
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 39
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 39
- 238000010898 silica gel chromatography Methods 0.000 claims description 39
- 125000003375 sulfoxide group Chemical group 0.000 claims description 39
- SZOLUXDHHKCYKT-ARJAWSKDSA-N (Z)-but-1-en-1-amine Chemical compound C(=C/CC)/N SZOLUXDHHKCYKT-ARJAWSKDSA-N 0.000 claims description 38
- 229910052760 oxygen Inorganic materials 0.000 claims description 38
- 239000001301 oxygen Substances 0.000 claims description 38
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 28
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 28
- 150000001875 compounds Chemical class 0.000 claims description 26
- BXMUVWKVQONWPP-UHFFFAOYSA-N acetic acid sulfane Chemical compound S.CC(O)=O.CC(O)=O BXMUVWKVQONWPP-UHFFFAOYSA-N 0.000 claims description 13
- APUPEJJSWDHEBO-UHFFFAOYSA-P ammonium molybdate Chemical compound [NH4+].[NH4+].[O-][Mo]([O-])(=O)=O APUPEJJSWDHEBO-UHFFFAOYSA-P 0.000 claims description 13
- 229940010552 ammonium molybdate Drugs 0.000 claims description 13
- 235000018660 ammonium molybdate Nutrition 0.000 claims description 13
- 239000011609 ammonium molybdate Substances 0.000 claims description 13
- 238000005352 clarification Methods 0.000 claims description 13
- 238000009413 insulation Methods 0.000 claims description 13
- 238000012544 monitoring process Methods 0.000 claims description 13
- 229920006395 saturated elastomer Polymers 0.000 claims description 13
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 claims description 13
- 235000019345 sodium thiosulphate Nutrition 0.000 claims description 13
- 239000007787 solid Substances 0.000 claims description 13
- 238000005303 weighing Methods 0.000 claims description 13
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 8
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 5
- WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 claims description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 abstract description 2
- 238000003912 environmental pollution Methods 0.000 abstract description 2
- 239000012634 fragment Substances 0.000 abstract description 2
- 229910052751 metal Inorganic materials 0.000 abstract description 2
- 239000002184 metal Substances 0.000 abstract description 2
- MGRWKWACZDFZJT-UHFFFAOYSA-N molybdenum tungsten Chemical compound [Mo].[W] MGRWKWACZDFZJT-UHFFFAOYSA-N 0.000 abstract description 2
- 231100000252 nontoxic Toxicity 0.000 abstract description 2
- 230000003000 nontoxic effect Effects 0.000 abstract description 2
- 229910000104 sodium hydride Inorganic materials 0.000 abstract description 2
- 239000012312 sodium hydride Substances 0.000 abstract description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 abstract 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 abstract 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 abstract 2
- -1 piperidine-1-yl-methylene Chemical group 0.000 abstract 2
- 238000006555 catalytic reaction Methods 0.000 abstract 1
- 238000002844 melting Methods 0.000 abstract 1
- 230000008018 melting Effects 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 208000025865 Ulcer Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 210000001035 gastrointestinal tract Anatomy 0.000 description 4
- 231100000397 ulcer Toxicity 0.000 description 4
- 229960001596 famotidine Drugs 0.000 description 3
- XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 description 3
- 208000007882 Gastritis Diseases 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- VNFPBHJOKIVQEB-UHFFFAOYSA-N clotrimazole Chemical compound ClC1=CC=CC=C1C(N1C=NC=C1)(C=1C=CC=CC=1)C1=CC=CC=C1 VNFPBHJOKIVQEB-UHFFFAOYSA-N 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 201000006549 dyspepsia Diseases 0.000 description 2
- 210000004051 gastric juice Anatomy 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 241000143437 Aciculosporium take Species 0.000 description 1
- 229940122957 Histamine H2 receptor antagonist Drugs 0.000 description 1
- 108010012944 Tetragastrin Proteins 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- XXRMYXBSBOVVBH-UHFFFAOYSA-N bethanechol chloride Chemical compound [Cl-].C[N+](C)(C)CC(C)OC(N)=O XXRMYXBSBOVVBH-UHFFFAOYSA-N 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000023652 chronic gastritis Diseases 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 230000027119 gastric acid secretion Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 239000003485 histamine H2 receptor antagonist Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- RGYLYUZOGHTBRF-BIHRQFPBSA-N tetragastrin Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)CCSC)C(N)=O)C1=CC=CC=C1 RGYLYUZOGHTBRF-BIHRQFPBSA-N 0.000 description 1
- 229940045137 urecholine Drugs 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
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CN201110115136.3A CN102276588B (zh) | 2011-05-05 | 2011-05-05 | 一种拉呋替丁的制备方法 |
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CN201110115136.3A CN102276588B (zh) | 2011-05-05 | 2011-05-05 | 一种拉呋替丁的制备方法 |
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CN102276588A true CN102276588A (zh) | 2011-12-14 |
CN102276588B CN102276588B (zh) | 2014-05-21 |
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102702181A (zh) * | 2012-06-29 | 2012-10-03 | 海南美兰史克制药有限公司 | 一种拉呋替丁化合物及其新制法 |
CN104557889A (zh) * | 2014-12-15 | 2015-04-29 | 广东东阳光药业有限公司 | 拉呋替丁异构体的制备方法 |
CN110642832A (zh) * | 2018-12-19 | 2020-01-03 | 安徽贝克生物制药有限公司 | 拉呋替丁及其中间体的制备方法和应用 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0282077A2 (en) * | 1987-03-13 | 1988-09-14 | Fujirebio Kabushiki Kaisha | Pyridyloxy derivatives |
WO2009090663A1 (en) * | 2008-01-15 | 2009-07-23 | Lupin Limited | Novel crystalline polymorph of armodafinil and an improved process for preparation thereof |
CN101747261A (zh) * | 2008-12-16 | 2010-06-23 | 浙江东亚药业有限公司 | 4-[4-(1-哌啶甲基)吡啶-2-氧]-cis-2-丁烯-1-醇的制备方法 |
-
2011
- 2011-05-05 CN CN201110115136.3A patent/CN102276588B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0282077A2 (en) * | 1987-03-13 | 1988-09-14 | Fujirebio Kabushiki Kaisha | Pyridyloxy derivatives |
WO2009090663A1 (en) * | 2008-01-15 | 2009-07-23 | Lupin Limited | Novel crystalline polymorph of armodafinil and an improved process for preparation thereof |
CN101747261A (zh) * | 2008-12-16 | 2010-06-23 | 浙江东亚药业有限公司 | 4-[4-(1-哌啶甲基)吡啶-2-氧]-cis-2-丁烯-1-醇的制备方法 |
Non-Patent Citations (2)
Title |
---|
J.PROUS,等: "lafutidine,Gastric antisecretory,antiulcerative,H2-Receptor antagonist", 《DRUGS OF THE FUTURE》 * |
KANEKO CHIKARA,等: "Photochemical ring opening reactions of 3- alkoxyisocoumarin and 3-halo-1-isoquinolone", 《HETEROCYCLES》 * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102702181A (zh) * | 2012-06-29 | 2012-10-03 | 海南美兰史克制药有限公司 | 一种拉呋替丁化合物及其新制法 |
CN104557889A (zh) * | 2014-12-15 | 2015-04-29 | 广东东阳光药业有限公司 | 拉呋替丁异构体的制备方法 |
CN104557889B (zh) * | 2014-12-15 | 2017-06-16 | 广东东阳光药业有限公司 | 拉呋替丁异构体的制备方法 |
CN110642832A (zh) * | 2018-12-19 | 2020-01-03 | 安徽贝克生物制药有限公司 | 拉呋替丁及其中间体的制备方法和应用 |
CN110642832B (zh) * | 2018-12-19 | 2022-09-30 | 安徽贝克生物制药有限公司 | 拉呋替丁及其中间体的制备方法和应用 |
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CN102276588B (zh) | 2014-05-21 |
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Owner name: SICHUAN KELUN PHARMACEUTICAL RESEARCH INSTITUTE CO Free format text: FORMER NAME: KELUN PHARMACEUTICAL RESEARCH CO., LTD. |
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CP03 | Change of name, title or address |
Address after: 611138 Sichuan science and Technology Development Zone, Wenjiang District, Chengdu City, Xinhua Road, the central section of the two paragraph Patentee after: SICHUAN KELUN DRUG RESEARCH INSTITUTE CO., LTD. Address before: 610500 Sichuan province Chengdu City satellite city industrial development zone two South Road Patentee before: Kelun Pharmaceutical Research Co., Ltd. |